Thyroid disorders

Question 1

Thyroid gland

Answer 1

A butterfly-shaped gland located in the neck, composed of two lobes connected by an isthmus. It is surrounded by a thin fibrous capsule of connective tissue.

Question 2

Structure of the thyroid

Answer 2

Thyroid epithelial cells line spaces called follicles, which are filled with colloid, a substance containing thyroid hormones. Parafollicular ‘c’ cells secrete calcitonin. Blood and lymph vessels, nerves and connective tissues are found between follicles.

Question 3

Function of thyroid hormones

Answer 3

Thyroid hormones are important for:

• control of metabolism
• regulation of growth
• multiple roles in development

Question 4

Control of thyroid secretion

Answer 4

Secretion of thyroid hormones is controlled by the hypothalamo-pituitary-thyroid axis. The hypothalamus secretes thyrotropin releasing hormone (TRH), stimulating the anterior pituitary to secrete thyroid stimulating hormone (TSH), which stimulates the thyroid to secrete T3 and T4.

Question 5

Synthesis of thyroid hormones

Answer 5

Thyroid hormones are synthesised in follicular thyroid cells. Iodine is absorbed from the bloodstream and concentrated in follicles, then bound to tyrosine residues on the thyroglobulin precursor molecule by the thyroperoxidase enzyme (TPO). This forms MIT and DIT, which are combined to make the active hormone triiodothyronine (T3) and the prohormone thyroxine (T4).

Question 6

De-iodination of T4

Answer 6

The biologically active thyroid hormone T3 is produced from the mono-deiodination of the prohormone T4, which is more abundant. Deiodinase enzymes are present in peripheral tissues.

Question 7

Hormone binding proteins

Answer 7

Thyroid hormones circulate in the bloodstream bound to proteins eg. thyroxine binding globulin (TBG), albumin, transthyretin. Only a very small percentage (T3=0.3%, T4=0.03%) circulates freely.

Question 8

Tests of thyroid function

Answer 8

• serum TSH
• serum free T3
• serum free T4

Question 9

Hyperthyroidism

Answer 9

Overactivity of the thyroid gland. Most commonly caused by Graves’ disease, toxic nodular goitre or thyroiditis. May also be caused by exogenous iodine, taking excess thyroid hormone, a TSH secreting pituitary adenoma, or neonatal hyperthyroidism. Prevalence is 10 times greater in females than in males.

Question 10

Signs and symptoms of hyperthyroidism

Answer 10

• cardiovascular; tachycardia, atrial fibrillation, shortness of breath, ankle swelling
• gastrointestinal; weight loss, diarrhoea, increased appetite
• neurological- tremor, myopathy (muscle weakness), anxiety
• eyes/skin- sore, gritty eyes, diplopia (double vision), staring eyes, pruritus (itching)

Question 11

Graves’ disease

Answer 11

The most prevalent autoimmune disorder in the UK, constituting 60-80% of cases of hyperthyroidism. Caused by a combination of genetic and environmental factors, with 50% of patients reporting a family history of the condition. Pathogenic antibodies bind to and stimulate TSH receptors on follicular thyroid cells, resulting in the oversecretion of thyroid hormones.

Question 12

Signs of Graves’ disease

Answer 12

• eyes; lid lag/retraction (staring), conjuctival oedema (swelling), periorbital puffiness, proptosis (bulging), opthalmoplegia (weakness of eye muscles)
• skin; pretibial myxoedema, acropachy

Question 13

Neonatal hyperthyroidism

Answer 13

Can occur when a mother has Graves’ disease/hyperthyroidism during pregnancy. Pathogenic TSH-R antibodies can cross the placenta, leading to a potentially very dangerous condition for the foetus.

Question 14

Diagnosis of hyperthyroidism

Answer 14

• low serum TSH
• high free T3 and T4
• clinical features eg. eye signs (50%), diffuse goitre (75-90%)
• thyroperoxidase antibodies (75%)
• TSH receptor antibodies (99%)
• isotope uptake scans using technetium/radioactive iodine

Question 15

Treatment of hyperthyroidism

Answer 15

• anti-thyroid drugs
• surgery
• radioactive iodine therapy

Question 16

Thionamides eg. carbimazole (methimazole), propylthiouracil

Answer 16

Anti-thyroid drugs which inhibit thyroperoxidase enzymes, blocking iodine incorporation and organification. Used as a short term solution to prepare patients for other treatment options, or to induce remission in Graves’ disease. Provides rapid control and is generally well tolerated, although side effects may include rashes, joint pains and sickness, as well as the rare incidence of agranulocytosis. Low cure rate (30-40%).

Question 17

Thyroidectomy

Answer 17

Surgery to remove the whole (total) or part of (partial) the thyroid gland. Complications include hypothyroidism, hypoparathyroidism, damage to the recurrent laryngeal nerve, bleeding, and the sudden release of lots of thyroid hormones into the bloodstream (thyroid storm, less common).

Question 18

I-131 therapy

Answer 18

Radioactive iodine therapy, in which a fixed dose of radiation is administered to the thyroid gland through a capsule of radioisotope. It is highly effective (85% cure rate), although may worsen eye disease and can carry risks of hypothyroidism, cancer and infertility. It is also contraindicated in pregnancy and breastfeeding.

Question 19

Hypothyroidism

Answer 19

Underactivity of the thyroid gland. Can be caused by Hashimoto’s thyroiditis, after treatment for hyperthyroidism, subacute/silent thyroiditis, iodine deficiency, and congenital anomalies (thyroid agenesis/ enzyme defects).

Question 20

Hashimoto’s thyroiditis

Answer 20

The most common cause of hypothyroidism in the UK, involving pathogenic antibodies to thyroperoxidase (TPO) and thyroglobulin (Tg). Causes inflammation of the thyroid and goitre, leading to fibrosis and shrinkage of the thyroid.

Question 21

Iodine deficiency

Answer 21

A major cause of goitre and hypothyroidism worldwide, particularly prevalent in mountainous and landlocked regions. Supplementation programmes aim to prevent malnutrition.

Question 22

Signs and symptoms of hypothyroidism

Answer 22

• cardiovascular; bradycardia, heart failure, pericardial effusion
• gastrointestinal; weight gain, constipation
• neurological; depression, psychosis, carpal tunnel syndrome
• skin; myxoedema, erythema ab igne, vitiligo

Question 23

Treatment of hypothyroidism

Answer 23

Levothyroxine is a drug which can be used to restore patients to a euthyroid state and normalise serum T4 and TSH levels.

Question 24

Congenital hypothyroidism

Answer 24

Arises when the thryoid fails to develop (agenesis), or when genetic abnormalities lead to enzyme defects. Characterised by cretinism, stunted growth and mental retardation. Newborns are screened using a heel-prick test.

Question 25

Goitre/thyroid nodules

Answer 25

Enlargement of the thyroid gland, which is extremely prevalent among the population (visible on ultrasound in 50-67%, palpable in 10%). Often found incidentally in patients undergoing imaging.

Question 26

Investigation of thyroid nodules

Answer 26

• assessment of thyroid function; serum TSH, free T3 and T4
• assessment of thyroid size; imaging (x-ray, CT, MRI), symptoms, respiratory flow loop
• assessment of thyroid pathology; radionuclide scanning, ultrasound, fine needle aspiration cytology

Question 27

Thyroid cancer

Answer 27

Forms are papillary, follicular, anaplastic and medullary carcinoma. Caused by irradiation, iodine deficiency, oncogene expression and genetic factors. Managed with surgery, radioiodine ablation, thyroxine suppression and measurement of serum thyroglobulin.

Question 28

Which transporter is responsible for the transport of iodine into thyrocytes?

Answer 28

Na+/I- symporter.